Buffering and the evolution of chromosome-wide gene regulation

Copy number variation (CNV) in terms of aneuploidies of both entire chromosomes and chromosomal segments is an important evolutionary driving force, but it is inevitably accompanied by potentially problematic variations in gene doses and genomic instability. Thus, a delicate balance must be maintained between mechanisms that compensate for variations in gene doses (and thus allow such genomic variability) and selection against destabilizing CNVs. In Drosophila, three known compensatory mechanisms have evolved: a general segmental aneuploidy-buffering system and two chromosome-specific systems. The two chromosome-specific systems are the male-specific lethal complex, which is important for dosage compensation of the male X chromosome, and Painting of fourth, which stimulates expression of the fourth chromosome. In this review, we discuss the origin and function of buffering and compensation using Drosophila as a model

Non-nociceptive roles of opioids in the CNS: opioids' effects on neurogenesis, learning, memory and affect.

Mortality due to opioid use has grown to the point where, for the first time in history, opioid-related deaths exceed those caused by car accidents in many states in the United States. Changes in the prescribing of opioids for pain and the illicit use of fentanyl (and derivatives) have contributed to the current epidemic. Less known is the impact of opioids on hippocampal neurogenesis, the functional manipulation of which may improve the deleterious effects of opioid use. We provide new insights into how the dysregulation of neurogenesis by opioids can modify learning and affect, mood and emotions, processes that have been well accepted to motivate addictive behaviours

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans

Engineering an incubation environment that mimics in situ conditions for in vitro coastal microbiome studies

 Table S1: Quality and taxonomic classification values of metagenomes analyzed in Figure 3. </p

Addressing Crystal Structure in Semiconductor Nanowires by Polarized Raman Spectroscopy

Raman scattering is a powerful inelastic light scattering technique able to probe the vibrational properties of materials. This technique has been successfully employed in semiconductor nanowires to provide information on their fundamental properties, such as the phononic properties, the crystal composition, and the electronic band structure. When performed in a polarization-resolved manner on a single nanowire, Raman spectroscopy can even allow addressing the nanowire's crystal structure. This is a fact of pivotal importance, as crystal phase is emerging as a novel degree of freedom in the bandgap engineering and phonon engineering of materials, and the control of the crystal phase is a possibility uniquely offered by nanowires. Indeed, recent advances in the synthetic growth of nanowires have given access to crystal phases (e.g., hexagonal phase in Si and Ge) that in the bulk can only be obtained under extreme pressure conditions, and it is possible to controllably switch between different crystal phases during the growth of nanowires. The realization and, even more, the interpretation of polarized Raman experiments on nanowires can be non-trivial, as several issues have to be considered. Therefore, in this chapter, we provide the basic theoretical background necessary to calculate Raman selection rules and interpret polarization-resolved Raman spectra of semiconductor nanowires. We also discuss the main ingredients of a Raman setup, with a focus on the scattering geometries typically used for nanowires. We highlight the main differences in the Raman spectra of nanowires with cubic and hexagonal crystal symmetries, and we treat also the case of the most challenging type of heterostructure: a nanoscale crystal-phase homostructure. Finally, we discuss resonant Raman experiments that allow the determination of the energy of some electronic transitions in nanowires. We focus mostly on a very new material system, namely Ge nanowires with controlled crystal phase, but the general procedure that we establish can be applied to several types of nanostructures

Efficacy of 5-Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials

BACKGROUND: Giardiasis is one of the most common causes of diarrheal disease worldwide and 5-nitroimidazoles (5-NI) are the most commonly prescribed drugs for the treatment of giardiasis. We evaluated the efficacy of 5-nitroimidazoles (5-NI) in the treatment of giardiasis in a systematic review of randomized controlled trials (RCTs). METHODOLOGY/PRINCIPAL FINDINGS: We conducted a comprehensive literature search in PubMed-Medline, Scopus, Web of Science and Cochrane Library for RCTs evaluating the efficacy of 5-NI vs. control (placebo or active treatment) on parasitological cure in patients with parasitologically-demonstrated giardiasis. The search was performed in May 2013 with no language restriction by two authors independently. The efficacy outcome was parasitological cure, and harmful outcomes were abdominal pain, bitter or metallic taste, and headache. We included 30 RCTs (n = 3,930). There was a significant and slightly higher response rate with 5-NI in giardiasis treatment (RR 1.06, 95%CI 1.02–1.11, p = 0.005). There was high heterogeneity among studies (I(2) = 72%). The response rates for metronidazole, tinidazole and secnidazole were similar (RR 1.05, 95%CI 1.01–1.09, p = 0.01; RR 1.32 95%CI 1.10–1.59, p = 0.003; and RR 1.18 95%CI 0.93–1.449, p = 0.18, respectively). On subgroup analyses, the response rates did not vary substantially and high heterogeneity persisted (I(2) = 57%–80%). Harmful outcomes were uncommon, and 5-NIs were associated with lower risk of abdominal pain, and higher risk of both bitter or metallic taste and headache. CONCLUSIONS: Studies investigating the efficacy of 5-NI in giardiasis treatment are highly heterogeneous. 5-NIs have a slightly better efficacy and worse profile for mild harmful outcomes in the treatment of giardiasis in comparison to controls. Larger high quality RCTs are needed to further assess efficacy and safety profiles of 5-NI